How to manage hypertriglyceridemia in a patient on high-intensity statin (HMG-CoA reductase inhibitor) therapy?

From the Guidelines

To manage high triglycerides in a patient already on high-intensity statin therapy, I recommend adding icosapent ethyl (Vascepa, 2 grams twice daily), as it has been shown to reduce major adverse cardiovascular events (MACEs) when added to moderate- or high-intensity statin therapy in patients with elevated triglycerides 1.

Management of Hypertriglyceridemia

The management of hypertriglyceridemia in patients on high-intensity statin therapy requires a multifaceted approach.

• Lifestyle modifications are essential and include limiting alcohol, reducing simple carbohydrates and sugars, increasing physical activity, and achieving weight loss if needed.
• Controlling diabetes with medications that don't increase triglycerides is important for diabetic patients.
• Before adding medications, secondary causes of hypertriglyceridemia should be ruled out, including uncontrolled diabetes, hypothyroidism, kidney disease, and certain medications 1.

Pharmacological Interventions

In addition to lifestyle modifications, pharmacological interventions may be necessary to manage hypertriglyceridemia.

• Icosapent ethyl (Vascepa, 2 grams twice daily) is a effective option for reducing triglycerides and has been shown to reduce MACEs when added to moderate- or high-intensity statin therapy in patients with elevated triglycerides 1.
• Fibrates, such as fenofibrate (145 mg daily) or gemfibrozil (600 mg twice daily), may also be considered, though gemfibrozil should be used cautiously with statins due to interaction risks.

Importance of Recent Evidence

The most recent evidence suggests that icosapent ethyl is a effective option for reducing triglycerides and MACEs in patients on high-intensity statin therapy 1.

• This study, published in 2021, provides the most up-to-date guidance on the management of hypertriglyceridemia in patients on high-intensity statin therapy.
• The study found that icosapent ethyl reduced MACEs by 25% compared to placebo in patients with elevated triglycerides and either established cardiovascular disease or diabetes with at least one other risk factor 1.

From the FDA Drug Label

The initial treatment for dyslipidemia is dietary therapy specific for the type of lipoprotein abnormality. Excess body weight and excess alcoholic intake may be important factors in hypertriglyceridemia and should be addressed prior to any drug therapy. Diseases contributory to hyperlipidemia, such as hypothyroidism or diabetes mellitus should be looked for and adequately treated. Estrogen therapy, thiazide diuretics and beta-blockers, are sometimes associated with massive rises in plasma triglycerides, especially in subjects with familial hypertriglyceridemia In such cases, discontinuation of the specific etiologic agent may obviate the need for specific drug therapy of hypertriglyceridemia.

To manage hypertriglyceridemia in a patient on high-intensity statin therapy, the following steps can be taken:

• Dietary therapy: Implement a lipid-lowering diet specific to the type of lipoprotein abnormality.
• Lifestyle modifications: Address excess body weight and excess alcoholic intake, and encourage physical exercise as an ancillary measure.
• Treatment of underlying diseases: Look for and adequately treat diseases that may be contributory to hyperlipidemia, such as hypothyroidism or diabetes mellitus.
• Discontinuation of etiologic agents: Consider discontinuing estrogen therapy, thiazide diuretics, or beta-blockers if they are associated with rises in plasma triglycerides. According to 2 and 2, fenofibrate can be used as an adjunctive therapy to diet for the treatment of adult patients with severe hypertriglyceridemia. The initial dose is 54 mg per day to 160 mg per day, and dosage should be individualized according to patient response.

From the Research

Management of Hypertriglyceridemia in Patients on High-Intensity Statin Therapy

To manage hypertriglyceridemia in patients on high-intensity statin therapy, several options can be considered:

• Dietary changes and physical activity to lower cardiovascular risk, including lowering carbohydrate intake and increasing fat and protein intake 3
• Calculating a patient's 10-year risk of atherosclerotic cardiovascular disease to determine the role of medications 3
• Considering high-dose icosapent (purified eicosapentaenoic acid) for patients at high risk who continue to have high triglyceride levels despite statin use 3
• Using fibrates, omega-3 fatty acids, or niacin for patients with severely elevated triglyceride levels to reduce the risk of pancreatitis 3

Omega-3 Fatty Acids as a Therapeutic Option

Omega-3 fatty acids, particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have been shown to be effective in reducing triglyceride levels:

• EPA and DHA dose-dependently reduce plasma triglyceride levels, with optimal doses of 3-4 g/day 4
• Prescription omega-3 fatty acid formulations, such as EPA+DHA or EPA-only, can reduce triglyceride levels by ≥30% and have been shown to be safe and effective as monotherapy or in combination with statins 5
• Omega-3 fatty acids may be a well-tolerated and effective alternative to fibrates and niacin for reducing triglyceride levels in patients with hypertriglyceridemia 6

Switching to Icosapent Ethyl

Switching from omega-3-acid ethyl esters to icosapent ethyl, a high-purity EPA ethyl ester, may result in beneficial changes in the lipid profile:

• A case study demonstrated a 41% reduction in triglyceride levels and additional reductions in LDL-C levels after switching to icosapent ethyl 7
• Icosapent ethyl may be a useful option for patients with persistently elevated triglyceride levels despite statin therapy 7